Ribose 5-deoxy-5-fluoro

Potassium fluoride in 1,2-ethanediol has further been used, as, for example, in the preparation of 5-deoxy-5-fluoro-D-ribose from methyl 2,3-0-isopropylidene-5-0-(methylsulfonyl)-a-D-ribofuranoside,87 and of 6-deoxy-6-fluoro-D-glucose from methyl 6-O-p-tolylsulfoiiyl-a-D-glucopyranoside.77 In one study of primary fluorinations with potas-... 

Deoxy-2-fluoro-D-ribose (83) has been prepared by fluorina-tion,2,8-220 hydrogenation, and hydrolysis of 2,2 -anhydro-( 1 -/3-D-ara-binofuranosyluracil) (82), followed, for purification purposes, by ben-zoylation of the resulting product, and hydrolysis221 (see also, Ref. 222). 

F]-5 -FDI 6a) and [ F]-5-fluoro-5-deoxy-D-ribose ([ F]-5-FDR 13a) has been achieved also in good radiochemical yields as shown in Scheme 10. 

The first step in this pathway involves SN2 displacement by fluoride on S-adenosine-L-methionine (SAM) catalyzed by the newly discovered enzyme fluor-inase (905-910), which also can function as a chlorinase (912). Fluorinase has been isolated and characterized, and the gene has been cloned (916). Both 5 -fluoro-5 -deoxyadenosine (847) and 5 -fluoro-5 -deoxy-D-ribose-l-phosphate (848) have been identified as intermediates (905-908). Fluoroacetaldehyde (850) is the immediate precursor, presumably via fluororibulose-1-phosphate (849) (915), to both fluoroacetate and 4-fluorothreonine (837) (901). The requisite enzymes fluoroacetaldehyde dehydrogenase (902) and L-threonine transaldolase-PLP (903) have been isolated and purified. The steps from 848 to 850 remain to be established but are based on known biochemistry. The pronounced toxicity of fluoroacetic acid... 

Fluoro-5-deoxy-D-ribose-l-phosphate as an Intermediate in Fluorometabolite Biosynthesis in Streptomyces cattleya. Chem Commun 592... 

Oligonucleotides containing 2 -deoxy-2 -fluoro-D-arabinose or -D-ribose form stable, triple-heUcal complexes stabilized by the intermolecular 2 -OH phosphate contacts and sugar puckering these derivatives have promoted interest in relation to compounds synthesized for DNA targeting in vivo Fig. 6 [31]. 

Modification of the 2 position of the ribose including 2 -0-methyl and 2 -deoxy-2 -fluoro have been shown to confer serum stability, while 2 -deoxy-2 -fluoro (2 -F) and locked nucleic acid (LNA where a methylene bridge connects the 2 -0 with the 4 -C of the ribose) have been shown to improve target binding affinity. 

NMR structure of a 2 -deoxy-2 -fluoro-D-arabinose (aF) nucleic acid duplex has been reported. The structure is a hybrid hairpin duplex containing a ribose-aF stem duplex and a four-residue DNA loop (177). The RNA strand adopted the classical A-form structure with endo sugar puckers, whilst the aF strand contained O -endo puckers and was intermediate between A- and B-form, similar to that found in DNA-RNA structures. 

Figure 9.4. Secondary structure of the 24-mer VPF/VEGF modified aptamcr. Pyrimidines (Y) all contained 2 -fluoro-2 -deoxy modifications, purines (R) with 2 -methoxy-2 -deoxy modifications are boxed purines (R) with unmodified ribose sugar residues are circled. The dissociation constant of the aptam-er/protein complex was 190 pM.

The first preparation of a secondary deoxyfluoro sugar, other than by total synthesis, involved the cleavage of 2,2 -anhydro-3-( 8-D-arabino-furanosyl) uracil (3) to give 3-(2-deoxy-2-fluoro-/3-D-ribosyl) uracil. This reaction, which can be extended to cleavage by hydrogen bromide or chloride, is at pr ent the only route to 2-deoxy-2-fluoro-D-ribose deriva-... 

Modified Oligonucleotides with Ability to Activate RNase H. Uniformly 2 -modified oligonucleotides are not capable of activating RNase H in an oligonucleotide/RNA hybrid. However, recent reports show that hybrids of RNA and arabinonucleic acids [the 2 -stereoisomer of RNA based on o-arabinose instead of the natural o-ribose (2 -arabino-OH, ANA) and 2 -deoxy-2 -fluoro-D-arabinonucleic acid (2 F-ANA)] are substrates of RNase H (358,359) (Fig. 5.9). However, ANA/RNA hybrids had a lower value, compared to that of the control DNA/RNA hybrids. This destabilization (AT, = -1.0°C/modification) is presumed to derive from steric interference by the -C2 -OH group, which is oriented into the... 

The magnitude of the fluorine—proton coupling constants have been invoked to establish the conformation of l,3,4-tri-0-benzoyl-2-deoxy-2-fluoro-jS-D-ribose as (66). The magnitude of the proton-proton... 

L-Xylose has been converted into a 2-deoxy-2-fluoro-P-L-arabinofuranose derivative, by way of a fluoride ion displacement of an imidazolylsulfonate, and then into a range of pyrimidine nucleosides. Displacement of another imidazolylsulfonate with Et3N.3HF initially formed the corresponding sulfonyl fluoride which was subsequently displaced by fluoride ion. Methyl 2,3-dideoxy-3-fluoro-5-0-(4-methylbenzoyl)-a-D-ribofuranoside, an intermediate for the syntheses of some anti-HIV nucleosides, has been synthesized from 2-deoxy-D-ribose in five steps and in 24% yield. ... 

The relative proportions of furanose and pyranose forms of aqueous 2-deoxy-2-fluoro-D-ribose at equilibrium have been determined with the help of H-, C-, and F-NMR spectroscopy.Recordings of vicinal C- P coupling constants were crucial for the determination of the configuration at phosphorus in the enantiomerically pure nucleoside phosphorothioates 40. After reassignment of the resonances for the phosphorus atoms in D-myn-inositol 1,2,6-trisphosphate, conclusions regarding the structure of its zinc complexes drawn previously on the basis of P-NMR titrations have been revised. 

A 2 -deoxy-2 -fluoro-p-D-ribofuranoside can be considered a substitute for the natural p-D-ribose in RNA as it favors a Ci -endo sugar pucker and A-type conformation when hybridised with RNA. However, 2 -fluoro containing oligonucleotides are not substrates for RNase and are inhibitors of... 

The synthesis of a series of 2 -fluoro-5-substituted arabinofuran-osyl-cytosines and -uracils has been described. 5-Methyluracil and 5-iodocytosine derivatives were the most effective against herpes simplex virus. The arabino configuration was essential for antibiotic activity, and corresponding chloro and bromo analogues were less effective.5 -Bromo-, 5 -fluoro-, and 5 -iodo-deriv-atives of 5-fluorouracil have been prepared conventionally. The a-anomer of 5 -fluoro-5 -deoxyuridine has been synthesized from a 1,2-oxazoline derivative of 5-deoxy-5-fluoro-D-ribose, in turn prepared by a sulphonate displacement using pyridinium fluoride. Treatment of 1-(o-D-arabinofuranosyl)-uracil with diphenylcarbonate yielded the 1,4-oxazin derivative (23) which yielded the 2 -chloro-2 -deoxy-arabino-a-nucleoside (24) on chlorination this was then reduced to the 2 -deoxy analogue (25). 5-Fluorouridine has been... 

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